Motor weakness and the compromised ability to walk following stroke have been the primary targets for testing interventions as there is a definite possibility of their improvement. Physical therapeutic interventions enhance recovery after stroke; however, the timing, duration and type of intervention require clarification and further trials. Pharmacotherapy, in particular with dopaminergic and selective serotonin-reuptake inhibitors, shows promise in enhancing motor recovery after stroke; however, further large scale trials are required. With increasing number of younger persons with stroke and an aging world population, the social as well as the economic burden of stroke on the health care systems will, in all likelihood, dramatically increase in future. Therefore, innovative methodologies for stroke rehabilitation are urgently required. These will influence, based on rational insights gained from neurophysiological studies, the cerebrospinal reorganization for restitution of gait function resulting from heterogenous post stroke deficits. Much of the research in the area of stroke has focused on recovery of walking. Walking is a basic human function, often affected by stroke, more easily observed, more easily measured and potentially more easily rehabilitated than other functional deficits.

The specific neurological mechanisms that mediate the neuromuscular recovery process after stroke are not completely understood. Evidence suggests that some motor recovery occurs because the auxillary cortical areas may take over functions. Two lines of research strongly support this statement: (1) Taub and Wolf reported convincing behavioural evidence from the forced-use paradigm; and, (2) Jenkins and Merzenich argued that cortical activity reorganizes with training and experience. [1],[2]

With the introduction of "movement related cortical plasticity" and "brain state dependent stimulation," closing the loop between the intrinsic state of the brain, the cortical stimulation and feedback from powered orthosis has given promising results for neuro-rehabilitation. It holds promise to invoke the Hebbian mechanism for a more efficacious neuroplasticity induction. Application of robot assisted neuro-rehabilitation in intensive goal directed movement repetition; and, automatic kinematic and kinetic data collection for improved outcome has been proven to be effective in the last 20 years. These techniques may allow highly impaired subjects to generate residual electromyography (EMG) to trigger the robot. Robotic training includes repeatability, precisely controllable assistance or resistance during movements, and objective and quantifiable measures of subject performance. The synchronization of afferent feedback with voluntary movements by a biological signal-triggered system is useful for motor recovery because synchronization between sensory and motor information facilitates neural plasticity. Pairing of rehabilitative training with non-invasive brain stimulation results in more enduring performance improvements and functional plasticity in the affected hemisphere compared with motor training or stimulation alone in patients with chronic stroke. The idea of extending a biofeedback loop of residual EMG directly to motor areas responsible for movement from a transcranial magnetic stimulation (TMS) pulse sits well with current opinions in neuro rehabilitation for enhanced motor learning. [1],[2],[3],[4]

The basis for the EMG triggered neuromuscular electrical stimulation assistance is that alternative motor pathways can be recruited and activated to assist the stroke-damaged efferent pathways. This theoretical explanation is based on the sensorimotor integration theory which states that sensory input from movement of the affected limb directly influences subsequent motor output. As post stroke individuals voluntarily attempt to extend their affected wrist and fingers, the EMG-monitored neuromuscular stimulation assists the movement and full extension is experienced. [3],[4]

Furthermore, pharmacotherapy may influence how the injured brain recovers. This complex array of influences and recent research increasingly confirm this concept. Many varied strategies and techniques are undergoing assessment including pharmacological therapy for aphasia, transcranial magnetic stimulation for motor recovery and cognitive rehabilitation for attention deficits. It is possible that when used in combination, these techniques may be symbiotic and synergistic. [1],[2]

Increasing evidence points towards improvement in performance of functional tasks with supervised training even in chronic stroke patients. Regular exercise after stroke leads to functional recovery which sustains for a long time. Some evidence has been published from India in the past. [5],[6] Exercise induces neurogenesis and angiogenesis through a growth factor cascade. Endurance exercise, i.e., running upregulates brain derived neurotrophic factors (BDNF) and synapsin 1mRNA (ribonucleic acid) which helps to facilitate better outcome in patients with stroke. Exercise preconditioning upregulates vascular endothelial growth factor (VEGF) which further regulates expression of matrix metalloproteinase (MMP2). MMP2 facilitates conversion of pro-nerve growth factor (NGF) and pro-BDNF into NGF and BDNF respectively. Altogether, this pro-angiogenic factor leads to the repair and restoration process of the post ischemic insult in the brain. Exercise also strengthens the microvascular integrity after cerebral ischemia and upregulates endothelial nitric oxide (NO) synthesis, which improves endothelium function by again upregulating VEGF expression. Early exercise after middle cerebral artery occlusion (MCAO) improves blood flow capacity in the ischemic cortex, reduces the infarct volume and promotes functional recovery. [4] Exercise therefore, modulates endogenous angiogenic mechanisms and exert its role in neurovascular remodeling mainly through VEGF which offers a potential breakthrough for development of new methods for long term recovery after stroke.

However, the study by Srivastava et al[7] in the current issue of Neurology India also reports definitive benefits with interventions 6 months post stroke. In their study, patients with chronic stroke were investigated for efficacy of rehabilitatitive interventions aimed at improving the performance of locomotor-related tasks. In these chronic stroke survivors discharged from stroke units, multiple outcome measures of walking ability, balance, functional disability and independence in performance of activities of daily living were measured. The authors were able to document a statistically significant improvement in the measured scales of outcome. This prospective repeated measure study indicated that chronic stroke survivors with impaired balance and gait who received 4 weeks of locomotor training showed better walking, balance and functional abilities both at the end of training and at 3 months of follow-up.

By developing interventions which can be administered several days, weeks or months after the onset of stroke, and which can essentially remodel the intact brain so as to compensate for the infarction, many more patients can be treated and brought back to their previous level of integration into the society as useful members.